CCR7 REGULATION OF IMMUNE AND NON-IMMUNE CELL ADHESION/MIGRATION

CCR7 对免疫和非免疫细胞粘附/迁移的调节

• 批准号: 7609894
• 负责人: CHARLOTTE M VINES
• 金额: $ 16.94万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609894
• 关键词: Adhesions; Biological Assay; Breast Cancer Cell; CD18 Antigens; CD29 Antigen; Cancer cell line; Cell Adhesion; Cells; Computer Retrieval of Information on Scientific Projects Database; Fibronectins; Funding; G-Protein-Coupled Receptors; Grant; Immune; Immune response; Immunologic Surveillance; Institution; Integrins; Liver; Lung; Lymphocyte; MCF7 cell; Mammary Neoplasms; Measures; Mediating; Modeling; Mus; Neoplasm Metastasis; Production; Proteins; Regulation; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Role; Site; Source; T-Lymphocyte; Testing; United States National Institutes of Health; Vascular Cell Adhesion Molecule-1; beta-Chemokines; bone; chemokine; chemokine receptor; lymph nodes; malignant breast neoplasm; migration; mouse model; novel; pathogen; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Following pathogen invasion, immune cells migrate to sites of chemokine production. C-C chemokine receptor 7, is a G protein-coupled receptor that controls lymphocyte migration to lymph nodes by regulating adhesion of primarily beta 1 and beta 2 integrins (heterodimeric transmembrane, adhesion proteins). Our initial studies confirmed CCR7 regulated beta 2 integrin adhesion of T-lymphocytes to LFA-1. Our novel findings revealed CCR7 differentially regulates beta 1 integrin adhesion and migration on fibronectin and VCAM. We have also observed that CCR7 regulates beta1 integrin adhesion in breast cancer cells. To extend our studies we hypothesized that CCR7 targets lymph node metastasis and mediates immune surveillance during metastasis. We are testing this hypothesis by expressing CCR7, in three mouse models of breast cancer ; (1) FVB model with PyVMT cells- which metastasize only to lung- to determine if CCR7 can alter targeting of metastases. (2) Balb/c mice with 4T1 cells- which metastasize to lung, liver, and bone to determine whether early expression of CCR7 and/or early arrival at lymph nodes can trigger a protective immune response. (3) Balb/c mice with 67NR cells- which form mammary tumors but fail to metastasize, to determine if CCR7 can induce metastases. To measure CCR7 in primary breast cancer cell isolates for our mouse studies, we are currently developing an RT-PCR assay and sequencing CCR7 in the established breast cancer cell lines: MDA-MB-231, MCF10A and MCF7. Overall, these studies will provide us with a better understanding of the role of CCR7 in the immune response and breast cancer progression to metastasis.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在病原体入侵后，免疫细胞迁移到趋化因子产生的位点。C-C趋化因子受体7是一种G蛋白偶联受体，通过调节主要β 1和β 2整联蛋白（异二聚体跨膜，粘附蛋白）的粘附来控制淋巴细胞向淋巴结的迁移。我们的初步研究证实了CCR 7调节T淋巴细胞与LFA-1的β 2整合素粘附。我们的新发现揭示了CCR 7差异调节β 1整合素在纤连蛋白和VCAM上的粘附和迁移。我们还观察到CCR 7调节乳腺癌细胞中的β 1整合素粘附。 为了扩展我们的研究，我们假设CCR 7靶向淋巴结转移并介导转移期间的免疫监视。我们通过在三种乳腺癌小鼠模型中表达CCR 7来测试这一假设：（1）具有PyVMT细胞的FVB模型-仅转移到肺-以确定CCR 7是否可以改变转移的靶向。(2)Balb/c小鼠与4 T1细胞-转移到肺，肝和骨，以确定是否CCR 7的早期表达和/或早期到达淋巴结可以触发保护性免疫反应。(3)Balb/c小鼠与67 NR细胞-形成乳腺肿瘤，但未能转移，以确定CCR 7是否可以诱导转移。为了在我们的小鼠研究中测量原发性乳腺癌细胞分离株中的CCR 7，我们目前正在开发RT-PCR测定法，并对已建立的乳腺癌细胞系：MDA-MB-231、MCF 10A和MCF 7中的CCR 7进行测序。总的来说，这些研究将使我们更好地了解CCR 7在免疫应答和乳腺癌转移进展中的作用。